1st Period Progress (extract from public summary)

In general the first period of the project was focussed on the development of clinical scenarios, the elaboration of system specifications, the development of both wearable and (bio)chemical sensors and the specification of the ICT security and communication framework. The project has put substantial emphasis on establishing a shared terminology and understanding of the mission, components and actors involved in each facet of the project. This is in particular important in projects involving many partners with different professional backgrounds. The project has therefore developed several easy-to-comprehend clinical scenario descriptions illustrating central aspects of the project to be developed. Further, a shared concept description has been developed and a vocabulary of d-LIVER technical and clinical terms has been defined. In all of this work, particular attention has been paid to establishing procedures for system quality, manufacturability and traceability according to international standards for medical devices.

One key task in the 1st period was commencing the formal evaluation of Quality-of-Life (QoL) in chronic liver disease patients living at home, and the factors impinging on it. Key issues are the impact of current management strategies and the degree to which the d-LIVER monitoring and support systems may be able to improve this situation. The study has been designed and Ethics approval has been obtained in the UK with an application prepared for submission in Germany.

Another goal was to complete a detailed study of the acceptability of the proposed approach by potential future d-LIVER users and to identify possible barriers to the uptake of the d-LIVER system in practice. With the input of patient groups (LIVErNORTH, UK and Deutsche Leberstiftung, Germany), clinical partners identified important potential issues concerning the d‑LIVER system. As a result, a first version of a questionnaire targeting the individual opinions of patients and carers on the proposed system was designed. The main focus was on familiarity with the use of novel technology, security of data transmission in the ICT setting, and acceptability of different levels of decision making (active/ passive decision support). In general, it was found that there was a broad acceptance of the d-LIVER concept among the target population.

Within the first period specifications and concepts for all the wearable physiological sensors and blood biochemistry sensors were defined and analytical characterization studies carried out, bearing in mind the suitability of the sensors for final integration into the overall d-LIVER systems. Currently, 8 out of the required 11 sensors are fully operational and most of these meet the requirements of the project in terms of performance. Further optimisation, improvement and integration will be continued in the 2nd period.

The ideal goal for the system is to be able to measure all eight blood biochemical parameters in a single microfluidic cartridge using a finger-prick blood sample. This commenced with microfluidic cartridge designs for various cases, including so-called ‘best case’ and ‘worst case’ fluidic scenarios. The scenarios outlined the need for new microfluidic functions, which would simplify the cartridge significantly. Accordingly, the development of the relevant microfluidic functions such as serum generation and dilution of liquids on chip was commenced. Initial work on sensor integration was also carried out.

Concepts for the integration of the different sensors for the online control of the bio-artificial liver support unit (BAL) were specified and developed. Fabrication processes were established that allowed integration of impedance sensors inside the BAL to monitor cell viability and quality. As a result, suitable parameters for the closed-loop control of cell culture conditions were specified and first measurement setups for the quality control of cells prior to their use in the BAL were established.

The instrument requirements and acceptance criteria have been clearly defined. The system design, that was originally planned for the 2nd period of the project, has already commenced.

In the 1st period concepts were developed for the Communication Architecture and Security Framework and for the Liver Patient Management System and Patient Client System. Bearing in mind that security is essential in systems dealing with medical information, an analysis of the security requirements for the d-LIVER architecture was performed as part of the security framework design. This security analysis covered different aspects, such as privacy, authentication, access control and security of communications. The mechanisms and techniques to achieve the required security level were based on international standards.

Within the work on a potential new source of hepatocytes for the BAL, a rat progenitor cell line which is readily expandable and produces quantitatively functional hepatocytes with a single hormone, was successfully seeded into an experimental bioreactor and differentiated into hepatocytes. The cells remained viable and functional for the length of the study. These pilot results demonstrated that it should be possible to produce bioreactors with functional human hepatocytes from an equivalent human progenitor.

The project website was launched and is updated regularly. Logos, clip-art, templates, and other dissemination materials were produced and distributed. Finally, a project factsheet and project overview slide were supplied to the Commission for dissemination purposes.